Research — GeneOps

rs358806 Regulatory variant near WNT5A linked to type 2 diabetes risk via impaired Wnt5a-mediated insulin secretion and adipose inflammation

Chromosome 3 Risk Allele C Category Fat Storage & Energy Tags Diabetes, Insulin, Energy Metabolism, Adipogenesis, Metabolic Health

WNT5A encodes a member of the Wnt family of secreted signaling proteins that operates primarily through non-canonical (β-catenin-independent) pathways. Inside the pancreas, Wnt5a acts as a direct regulator of insulin secretion; in adipose tissue, the same molecule becomes a pro-inflammatory driver when its natural...

rs3803304 Intronic AKT1 variant near a conserved exon-intron boundary; the G allele is associated with elevated AKT phosphorylation activity and reduced probability of exceptional longevity in centenarian studies

Chromosome 14 Risk Allele G Category Longevity & Aging Tags Longevity, Aging, Insulin, Cardiovascular, Cancer Risk, Inflammation

AKT1 (also called protein kinase B, or PKB) is a master regulator sitting at the center of the insulin and IGF-1 signaling cascade — the most evolutionarily conserved longevity pathway known, from roundworms to humans. When insulin or IGF-1 binds its receptor, PI3K activates and recruits AKT1 to the cell membrane,...

rs4988321 Missense variant in LRP5 that substitutes valine for methionine at position 667, modestly reducing Wnt signaling and lowering bone mineral density — particularly in physically active individuals

Chromosome 11 Risk Allele A Category Fitness & Body Tags Bone Health, Bone & Joint, Osteoporosis, Fracture Risk, Calcium, Vitamin D

Your skeleton is in a constant state of renovation. Every day, old bone is broken down by osteoclasts and replaced by new bone laid down by osteoblasts. What governs this process? In large part, a signaling cascade called the Wnt pathway(https://pubmed.ncbi.nlm.nih.gov/11823643/). LRP5 (low-density lipoprotein...

rs587782951 Pathogenic missense variant in junctophilin-2 that disrupts sarcoplasmic reticulum coupling and calcium signaling, causing hypertrophic cardiomyopathy with high age-dependent penetrance

Chromosome 20 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Heart Disease, Cardiovascular, Calcium, Genetic Counseling, Muscle, Carrier Status

Your heart muscle relies on millisecond-precise calcium pulses to contract and relax in perfect rhythm. The junctophilin-2 protein, encoded by JPH2, is the structural bridge that makes this possible — a molecular tether clamping the plasma membrane and sarcoplasmic reticulum together so that the electrical signal...

rs6420424 Upstream regulatory variant near BCO1 that reduces beta-carotene to vitamin A conversion efficiency by approximately 59%

Chromosome 16 Risk Allele A Category Vitamins & Nutrient Absorption Tags Vitamin A, Beta-Carotene, Diet, Food Sensitivity

The BCO1 gene encodes beta-carotene 15,15'-monooxygenase(), the single enzyme responsible for converting plant-derived provitamin A into a form the body can use. Most of the genetic variation in beta-carotene conversion has been attributed to two coding variants in BCO1 — rs7501331 (Ala379Val)() and rs12934922...

rs7047299 Regulatory variant upstream of interferon alpha-21 associated with increased susceptibility to herpes zoster (shingles) via reduced type I interferon antiviral signaling

Chromosome 9 Risk Allele A Category Innate Immunity & Infection Defense Tags Innate Immunity, Interferon, Infectious Disease, Viral Clearance, Immune Defense, Vaccination

Herpes zoster — shingles — is not a new infection. It is varicella-zoster virus (VZV) waking up after decades of dormancy in your dorsal root ganglia, the nerve cell clusters flanking your spinal cord. Almost everyone who had chickenpox as a child carries the virus for life. Whether it stays dormant or breaks...

rs71785313 Six-base-pair in-frame deletion removing two amino acids from apolipoprotein L1, conferring trypanosome resistance but dramatically increasing chronic kidney disease risk in homozygous or compound heterozygous state with G1

Chromosome 22 Risk Allele D Category Cholesterol & Lipoproteins Tags Kidney Disease, Cardiovascular, Infectious Disease, Ancestry, Lipid Metabolism

The APOL1 gene encodes apolipoprotein L1(https://omim.org/entry/603743). APOL1 protein forms ion channels in the trypanosome membrane, killing the parasite. But Trypanosoma brucei rhodesiense evolved a countermeasure — the serum resistance-associated (SRA) protein(https://www.nature.com/articles/nature12516),...

rs74315329 Pathogenic nonsense variant in myocilin causing autosomal dominant juvenile and adult-onset open-angle glaucoma through trabecular meshwork dysfunction and elevated intraocular pressure

Chromosome 1 Risk Allele A Category Coronary Artery Disease & Atherosclerosis Tags Glaucoma, Eye Health, Cardiovascular, Genetic Counseling, Endothelial Health

Glaucoma is the leading cause of irreversible blindness worldwide, affecting over 80 million people. Most cases are "open-angle" — the drainage angle of the eye looks normal under examination, yet fluid builds up and silently crushes the optic nerve over years. For a small but well-defined group of patients, the...

rs8034191 Intronic variant near CHRNA3 at 15q25.1 that acts as an eQTL for nicotinic receptor genes and is independently associated with heavy smoking and lung cancer risk

Chromosome 15 Risk Allele C Category Mood & Behavior Tags Mental Health, Addiction, Smoking, Lung Cancer, Neurotransmitters

On chromosome 15, a busy stretch of DNA called 15q25.1 houses a cluster of nicotinic acetylcholine receptor genes — CHRNA5, CHRNA3, and CHRNB4 — plus several neighboring genes including AGPHD1 (also known as HYKK, hydroxylysine kinase). The rs8034191 variant sits in the third intron of AGPHD1, just upstream of the...

rs8087522 Upstream regulatory variant near MC4R that may create a transcription factor binding site, with emerging evidence linking the A allele to greater weight gain during clozapine treatment

Chromosome 18 Risk Allele A Category Appetite & Obesity Tags Appetite, Obesity, Metabolic, Pharmacogenomics, Energy Metabolism, Drug Response

The melanocortin-4 receptor (MC4R) is the central satiety switch in the brain's hypothalamic energy balance circuit(). When the MC4R pathway is working, leptin from fat cells activates POMC neurons that release alpha-melanocyte stimulating hormone (α-MSH), which binds MC4R receptors and sends "stop eating" signals....